| Autor: |
Schmitt, Estelle, Steyaert, Alain, Cimoli, Guido, Bertrand, Richard |
| Předmět: |
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| Zdroj: |
Cell Death & Differentiation; Jun98, Vol. 5 Issue 6, p506, 11p |
| Abstrakt: |
Stable transfected human p53 (mt/mt) B lymphoma Namalwa variant lines showing differential expression of the Bax-α protein were derived under hygromycin selection. Overexpression of Bax-α in these variant cells accelerates cell death induced by short or continuous treatments with various concentrations of camptothecin, etoposide, vinblastine and shows no accelerating cell death activity in cis-platinum and paclitaxel-treated cells. Activation of apoptosis and oligonucleosome-sized DNA fragmentation was observed in the variant lines with more pronounced effect in cells containing high level of Bax-α protein. These results suggest that increased cell death mediated by anticancer drugs correlates with Bax-α level of expression and that Bax-α sensitizes Namalwa cells treated at low drug concentrations. The extent of DNA synthesis inhibition following DNA topoisomerase inhibitor treatments was similar in control and all transfected Namalwa cells suggesting that Bax-α acts downstream of DNA topoisomerase-mediated DNA strand breaks. To define further the relation between Bax-α expression and apoptosis activation, kinetics of caspase activation was measured in drug-treated cells. Caspase activities were measured using specific fluorogenic peptide derivatives DABCYL-YVADAPVEDANS and Ac-DEVD-AMC, substrates of the caspase 1-like and caspase 3-like families, respectively. In control and Bax-α transfected Namalwa cells no increase in caspase 1-like activity was detected following camptothecin and etoposide treatments. In contrast, a significant difference in Ac-DEVDAMC hydrolysis activity was observed in Bax-α transfected Namalwa cells compared to that of control Namalwa cells after camptothecin and etoposide treatment. Increased caspase 3like activity correlated also with poly(ADPribosyl) polymerase cleavage. Taken together, these results suggest that Bax-α sensitize B lymphoma cells to series of anticancer drugs... [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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